3. objectives
 Overview
 Historical aspect
 Acute inflammation
 Mediators of inflammation
 Morphologic Patterns of Inflammation
 Outcomesof Acute Inflammation
 Chronicinflammation
 Systemiceffects on inflammation
 Consequence of Defective Inflammation
 Implicationof inflammationin medical practice

4. INFLAMMATI
ON
Protective
Mechanism
Tissue damage
Necrotic
tissue
Foreign
Invader
Plasma
protein
leukocyte phagocytes
Types
Acute
chronic
B
U
T
adly
ncontrolled
riggered
Inflammatory Response
TISSUE
INJURY

7.  In 3000 BC Egyptian Papyrus
 Celsus (Roman Writer)- 1st century AD- listed four
cardinal signs
 Rubor (Redness)
 Tumor (Swelling)
 Color (Heat)
 Dolor(Pain)
 In 19th century Rudolf Virchow
 FunctioLaesa
More Prominent in ACUTE
INFLAMMATION

8.  JULIUS COHNHEIM (1839- 1884) provided
one of the first microscopic descriptions of
inflammation.
 The Russian biologist ELLIE METCHNIKOFF
discovered the process of PHAGOCYTOSIS by
observing the ingestion of rose thorns by
amebocytes of starfish larvae (1882) & of
bacteria by mammalian leukocytes (1884).

9.  SIR THOMASLEWIS : establishedthe conceptthat chemical
substances, locally induced byinjury, mediate thevascular
changesof inflammation.(1924)
 The reactionso elicitedis known as TRIPLERESPONSEor
REDLINERESPONSE consisting of following:
 Redline:appears withina few seconds followingstroking & results
from local vasodilation of capillaries& venules.
 Flare:is the bright reddish appearance or flush surrounding the
redline & results from vasodilation of adjacent arterioles.
 Wheal:is the swellingor edema of the surrounding skin occurring
due to transudation of fluidinto the extravascular spaces.

11. ‘Inflammation is a localized protective response elicited
by injury or destruction of tissues which serves to
destroy , dilute or wall off both the injurious agent and
injured tissue .’
Medical dictionary of pathology

13. characteristic
 RapidHostResponse
 Alterationsinvascularcalibre
 Increasebloodflow
 Structuralchangesinmicrovasculature
 Plasmaprotein&Leukocyteleavecirculation
 Emigration
 Leukocyte
 Toaccumulateininjuriousfoci
normal
inflamed

14. • Bacterial, viral, fungal,
parasitic
• ischemia, trauma, chemical injury
• release uric acid, ATP, DNA-binding protein
• Hypoxia – HIF-1α – VEGF – permeability –
inflammation
 hyper sensitivity reaction
Auto-immune disease
Immune mediated
inflammatory disease
INFLAMATION

15.  Connective
tissue cells
Mast cells
Macrophages
Fibroblasts
 Connective tissue
matrix
Elastic fibers
Collagen fibers
Proteoglycans
Vessels Soluble
proteins
Neutrophils Complement
Eosinophils Coagulation
Platelets Kinin system
Monocytes
Lymphocytes

17.  Changes in vascular flow and
caliber
 Vasodialation
 Induce by – histamine, NO
 Increase blood flow– heat &
redness
 increase RBC concentration
 Vascular congestion of small
vessels – localized redness
 Increased vascular
permeability

18.  Hallmark of acute inflammation
 Accomplished by the following steps
 Contraction of endothelial cells –
increase interendothelial space
 Mediated by – histamine, bradykinin,
substance-p
 Endothelial injury – cell necrosis and
detachment
 Sometimes neutrophils that adhere to
endotheliam – may injure endothelium
– thus amplify the tissue reaction
 Increased transport of fluid and
protein – transcytosis

19. •
•
•

20.  Lymph flow is increased
 Drains edema fluid that accumulate at extra
vascular space
 Lymph channels proliferate to control the
edema
 Painfull enlargement of draining lymph
node – LYMPHADENITIS
 Secondarily infected lymphatics –
LYMPHANGITIS
 TELLTALE sign
 red streak near wound
 indicative of infection
 involvement of lymphatics

21. Reaction of LEUKOCYTES in
inflammation
 Inflammation causes migration of
leukocytes from vessels to site of injury.
 This recruitment accomplish by the
following steps
 In the lumen – margination, rolling, adhesion
 Migration across endothelium
 Migration toward the site of injury by
chemotaxis

23.  Blood flow reduces at early stage of inflammation
 Redistribution of leukocyte along the endothelium
 Leukocyte – adhere – detach – bind = Rolling
 Mediated by
 Cytokines
 TNF, IL-1, Chemokines
 Selectin
 L-selectin
 E-selectin
 P-selectin
Responsible for rolling

24.  Progressively rolling action slows
down
 Bind firmly with endothelium
 Mediated by – Integrins
 TNF & IL-1 induce expression of
Integrins
 Chemokine activate rolling
leukocyte
 Cytokine induced integrin binds
with leukocyte to produce firm
adhesion to the endothelium

25.  Leukocyte Migration through
Endothelium













27.  Leukocyte moves by extending a pseudopod
 Network of filaments in the interior of pseudopods
 Locomotion involves rapid assembly of actin monomers into linear polymers at pseudopod
ledging edge
 Cross-linking of filaments
 Disassembling of filaments away from the ledging edge
 These events are controlled by Calcium
ions and Phosphoionositol on actin
regulating proteins -filamin, calmodulin.
 These components interact with actin
and myosin in pseudopod to produce
contraction

31. Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
Heat (calor)
Redness (rubor)
Swelling (tumor)
Pain (dolor)
Physiological Symptoms
Responses

33. Mediators of inflammation
Mediators Principal sources Actions
CELL DERIVED
Histamine Mast cell, basophil,
platelet
Vasodilation , increased vascular
permiability, endothelial activation
Serotonin Platelets Vasodilation , increased
permeability
Prosta glandin Mast cell, leukocyte Vasodilation, pain, fever
Leukotrienes Mast cell, leukocyte Chemotaxis, leukocyte adhesion &
activation
Platelet- activating factor Leukocyte, mast cell Degranulation, Oxidative burst
Reactive Oxygen Species Leukocyte Microbicidal, Tissue damage
Nitric Oxide Endothelium,
Macrophages
Vascular smooth muscle relaxation
Cytokine ( TNF, IL-1)
Chemokines
Macrophage, mast cell
leukocyte
Local endothelial activation
Chemotaxis, leukocyte activation

34. Mediator Principal source Functions
PLASMA PROTEIN
DERIVED
Complement Products
(C5a, C3a, C4a)
Plasma (produced in liver)
Leukocyte chemotaxis and
activation, vasodialation
Increased permeability,
smooth muscle contraction
Endothelial activation,
leukocyte recruitment
Kinins Plasma (produced in liver)
Protease activated during
coagulation
Plasma (produced in liver)

37. Platelet Activating Factor
Also synthesize other mediators like Eicosonoids by leukocytes and other cells
Causes Vasoconstriction and Bronchoconstriction
Regulated by Acetyl hydrolases
PAF mediates its effects via single G-protein coupled receptor
Bioactive phospholipid derived mediator

41. systems

42. Complement system

44. Systemic effects of acute inflammation
 Fever
 Leucocytosis (15-20,000)
Bacterial infection- Neutrophilia
Viral infection -Lymphocytosis
Parasitic infection- Eosinophilia
 Hypotension
 Increased ESR and C-reactive protein

51. Classification of Inflammation
 BASED ON EXUDATE
 Suppurative (purulent) inflammation
 Serousinflammation
 Catarrhal inflammation (inflammation of mucous membranes)
 Fibrinous inflammation: fibrinogen -fibrin
 Pseudomembranous inflammation: surface necrosis
 Necrotizing inflammation
 Hemorrhagic inflammation
 Ulcerative inflammation
 BASED ON HISTOLOGICAL FEATURE
 BASED ON CAUSATIVE AGENT

52. Based on EXUDATE
 Suppurative (purulent)
inflammation: pus
 Localized proliferation of pus-forming
organisms, such as Staphylococcus aureus
(e.g., skin abscess).
 S. aureus contains coagulase. which
cleaves fibrinogen into fibrin and traps
bacteria and neutrophils
 Pyogenic bacteria, eg, staphylococci,
streptococci, gram–negative bacilli,
anaerobes.

54.  Serous inflammation: (effusion)
 Thin, watery exudate
 Insufficient amount of fibrinogen
to produce fibrin

 Example -blister in second-degree
burns, viral pleuritis

55. EXUDATE TRANSUDATE
 Caused by inflammation
 High protein content
 Specific gravity high
 Generally associated with
infection
 caused by disturbances
of hydrostatic or colloid osmotic
pressure
 Less protein content
 Specific gravity less
 Generally associated with thermal
or chemical injury
Rivalta’s test:: is a very simple, inexpensive method that does not require special laboratory
equipment and can be easily performed in private practice. This test was originally developed by
the Italian researcher Rivalta around 1900 and was used to differentiate transudates and exudates
in human patients.
A test tube is filled with distilled water and acetic acid is added. To this mixture one drop of the
effusion to be tested is added. If the drop dissipates, the test is negative, indicating a transudate.
If the drop precipitates, the test is positive, indicating an exudate

56.  Catarrhal inflammation (inflammation of mucous
membranes)
 Marked secretion of mucus.
 Infections, eg, common cold (rhinovirus); allergy (e.g. hay
fever)

57.  Fibrinous inflammation: fibrinogen -fibrin
 Due to increased vessel permeability. with deposition of
a fibrin-rich exudate
 Often occurs on the serosal lining o f the pericardium,
peritoneum, or pleura
 Danger of adhesions
 Example: fibrinous pericarditis

58. Pseudomembranous inflammation:
surface necrosis
 Bacterial toxins damage mucosal lining, producing a
membrane composed of necrotic tissue
 Example ― pseudomembranes associated with Corynebacterium
diphtheriaeproduces a toxin causing pseudomembrane formation in the pharynx
and trachea.

59.  Necrotizing inflammation:
 Marked tissue necrosis
 Highly virulent organisms (bacterial, viral, fungal)
 Eg, plague (Yersinia pestis), anthrax (Bacillus anthracis),
mucormycosis, maxillofacial gangrene (noma).

60.  Hemorrhagic inflammation:
 Destruction of blood vessel walls resulting in leakage of a
large number of red blood cells resulting in the red
coloration of inflammatory exudate.
 Example ― Epidemic hemorrhagic fever, Leptospirosis and
Plague

61.  Ulcerative inflammation:
 Necrosis on or near the surface leads to loss of tissue and
creation of a local defect (ulcer)
 Example ― Ulcerative gingivitis

62.  Nonspecific:
 Produce non-specific histologic picture
 Specific:
 Produce a specific histologic picture that is peculiar to
that type of infection e.g. TB.

63.  Aseptic(sterile)
 chemical substances, radiation
 Septic
 (caused by living organisms)

65.  Is the persistence of inflammation with attempts
of repair resulting from persistence of the
injurious agent.

66.  Persisting infection or prolonged exposure to irritants
(intracellular surviving of agents -TB)
 Repeated acute inflammations (otitis, rhinitis)
 Primary chronic inflammation -low virulence, sterile
inflammations (silicosis)
 Autoimmune reactions (rheumatoid arthritis,
glomerulonephritis, multiple sclerosis)

67. Mechanism......
 Defective acute inflammatory response
 Poor blood supply
 Poor general nutrition
 Abnormal neutrophil function
 Anti-inflammatory drugs, especially corticosteroids
 Agent is resistant to phagocytosis and/or intracellular destruction
 Intracellular infectious agents, e.g. tuberculosis, salmonellosis, brucellosis, viral
infections
 Foreign-body reactions
 The provoking agent is a body constituent as in:
 Auto-immune diseases, e.g. diffuse lymphocytic thyroiditis (Hashimoto’s
disease), auto-immune atrophic gastritis, adrenal atrophy, etc.
 Reactions to altered self-antigens, e.g. contact dermatitis to rubber, nickel, etc

68.  Continuing some features of acute inflammation
 Polymorph infiltration
 Fibrinous exudation
 Increased vascularity
 Features of healing-repair and/or regeneration
 Infiltration by chronic inflammatory cells
 Lymphocytes
 Plasma cells
 Macrophages
 Eosinophils

70. Granulomatous inflammation
 A distinct pattern of chronic inflammation
characterized by formation of granulation tissue.
 It is a protective response to chronic infection or
foreign material, preventing dissemination and
restricting inflammation.
 Some autoimmune diseases such as rheumatoid
arthritis and Crohn’s disease are also associated
with granulomas

71. ? Granuloma.......
 A granuloma is a localized mass of granulation tissue with aggregations
of chronic inflammatory cells
 The granuloma consists of a kernel of infected macrophages
surrounded by foamy macrophages and a ring of lymphocytes and a
fibrous cuff.

73. Causes of granuloma......
 Bacteria:
 Tuberculosis, Leprosy, Syphilis, Actinomycosis
 Parasites:
 Schistosomiasis
 Fungi:
 Histoplasmosis, Blastomycosis
 Foreign bodyGranulomas
 Endogenous
 keratin, necrotic bone or adipose tissue uric acid crystals
 Exogenous
 wood, silica, asbestos, silicone
 Unknown cause such as sarcoidosis

75. Ascitis / Hydroperitonium
 Accumulation of fluid in peritoneal cavity
 Classification
 G-I – mild
 G-II – detectable with flank bulging & shifting dullness
 G-III – directly vbissible
 Cause
 Transudative
 Cirrhosis
 Heart failure
 kwashiokor
 Exudative
 Cancer ( primary / Metastatic)
 Tuberculosis
 Pancreatitis
 serositis
 Treatment
 Pharmacological
 Diuretics – aldosteron / spironolactone / furosemide
 Non-pharmacological
 Fluid tapping

76.  Inflammation of pleural layer
 Inflamed layer rub together to
cause pain
 Symptom
 Dry cough, fever, shortness of
breath, rapid pulse
 Collection of fluid in pleural space
 Cause
 Auto-immune disease – SLE/ RA
 Pneumonia, Tuberculosis
 Pulmonary Embolism
 Management
 Putting Chest Drain

79.  Inflammatory reaction is greater in diabetic status
 Conversely local inflammation causes intensification of
diabetes
 According to Russel in 1966
 Cellular dehydration
 Loss of alkali reserve
 Vessels lumen get obliterated
 Thickening of capillaries - Role in inflammation acts as a barrier to
leukocytic emigration into site (Brayton et al 1970)

84. Role of surgical drain
 After surgery, have to put one or two drains, called a Jackson-Pratt
(JP) drain, placed near the incision.
 This device collects fluid, under suction, from your surgical area.
 The drain promotes healing and recovery, and reduces the chance of
infection.
 The drain will be in place until the drainage slows enough for your body
to reabsorb fluid on its own.
 The tube may be removed once a single tube output is less than 30cc
(1 oz.) in 24 hours.

86. NSAIDs: Drug Effects
 Analgesic (mild to moderate)
 Anti-gout
 Anti-inflammatory
 Antipyretic
 Relief of vascular headaches
 Platelet inhibition (ASA)

87. Role in inflammation

88. NSAIDs Adverse Effects
 Platelet Dysfunction
 Gastritis and peptic ulceration with bleeding (inhibition of PG
+ other effects)
 Acute Renal Failure in susceptible
 Sodium+ water retention and edema
 Analgesic nephropathy
 Prolongation of gestation and inhibition of labor.
 Hypersenstivity (not immunologic but due to PG inhibition)
 GIT bleeding and perforation

89. Role of seratiopeptidase
 Serratiopeptidase is an enzyme isolated from a non-pathogenic bacteria called
enterobacteria Serratia E15
 Serratiopeptidase has powerful anti-inflammatory properties and is particularly
useful for post-traumatic swelling, fibrocystic breast disease and bronchitis. It
is able to digest dead tissue, blood clots, cysts, and arterial plaques. Clinical
studies have shown it to be effective at reducing swelling and edema and
metabolizing scar tissue in the body.
 A 2003 study found that 30mg of serratiopeptidase was effective at loosening
and reducing mucous build-up in respiratory pathways. This was credited to its
ability to reduce the neutrophil white blood cell numbers and to improve the
viscoelasticity of the sputum in patients with chronic airway disease.
 A 2006 study looked at the role serratiopeptidase has on improving immunity
 studies have shown similar anti-inflammatory effects after oral surgery was
performed

90.  Trypsin –chymotrypsin --- proteolytic enzyme
 When an injury occurs, the body responds with an inflammatory cascade.
Excessive inflammation can retard the healing process.
 Proteolytic enzyme supplementation reduces inflammation by
neutralizing bradykinins and pro-inflammatory eicosanoids to levels
where the synthesis, repair and regeneration of injured tissues can
begin.
 Proteolytic enzymes do not completely inhibit all phases of the
inflammatory cascade to a point where the body is unable to trigger the
normal healing process.
 Low-dose chymotrypsin treatment inhibits neutrophil migration into
sites of inflammation in vivo: Effects on Mac-1 and MEL-14 adhesion
protein expression and function

92. Chemical Make-Up
 Hydrocortisone or cortisol is the primary agent
 Glucocorticoid, which is naturally secreted by body is
derivative
 Currently, many AI steroids are available more powerful than
cortisol, but have the same chemical structure as glucocorticoid
 Long term use will inhibit body’s glucocorticoid activity and
the body’s ability to produce this substance naturally

93. How it Works

94. Time Action Profile
Drug Onset Peak Duration Half Life
Cortisone PO rapid 2 hrs 1.25-1.5
dys
8-12 hrs
Cortisone IM slow 20-48
hrs
1.25-1.5
dys
Prednisolone
PO
UK 1-2 hrs 1.25-1.5
dys
18-36
hrs

95. Adverse effect of corticosteroids
 Receive long-term, high-dose steroid
 Hypertension, heart failure
 Osteoporosis, DM, impaired wound healing, metal depression
and psychosis
 Peptic ulcer, Cataract, glaucoma, growth suppression,
hypocalcemia, PTH increased
 Cushing syndrome
 Secondary adrenal insufficiency

96.  interferon-γ (IFN-γ) constitutes a positive factor triggering or promoting the inflammatory response
 Systemic interferons, fulfil a down-regulating role, as evidenced by the observation that
exogenously administered IFN-α, -β, and -γ inhibit local inflammation.
 type I interferons (IFNs), IFN-α and IFN-β, are cytokines that have antiviral, antiproliferative, and
immunomodulatory activities
 Type I IFNs, through their ability to induce the immunosuppressive cytokine interleukin-10 (IL-10),
mediate the inhibition of pro-inflammatory gene products.
 In addition, type I IFNs induce other immunosuppressive mediators such as suppressor of cytokine
signaling–1 (SOCS-1) and tristetrapolin (TTP), which act by divergent mechanisms to restore
homeostasis to the immune system.
 Furthermore, type I IFNs mediate anti-inflammatory and protective effects in a variety of autoimmune
disease

97. Dimethyl Sulfoxide (DMSO)
Drug of question - used with
animals and to clean floors
Highly effective in the reduction of
edema
Clinical trials inconclusive or were
stopped (changes in eyes)

98. DMSO
 FDA approved 50% solution for TX of cystitis
 Canada approved 70% solution for TX of Scleroderma
 Vets approved 90% solution for TX of edema
 Public gets 99% industrial solution approved for
degreasing

103. conclusion
 Humans owe to inflammation & repair their ability to
contain injuries & heal defects. Without
inflammation, infections would go unnoticed, would
never heal, & injured organs might remain permanent
festering sores. However inflammation & repair may be
potentially harmful

104. refferences
 Basics of Pathology, Robins & Cotrans
 Pharmacological basis of theraputic, Goodman-Gillman
 Essentials of medical pharmacology, KD Tripathi
 Oxford hand book of clinical medicine, 8th edition
 Reducing Inflammation with Proteolytic Enzymes, Part One: Absorption and
Sources ;By G. Douglas Andersen, DC, DACBSP, CCN
 Dynamic Chiropractic – July 12, 1999, Vol. 17, Issue 15 Reducing Inflammation with
Proteolytic Enzymes, Part One: Absorption and Sources;By G. Douglas Andersen, DC,
DACBSP, CCN
 Cellular Immunology, vol.132 issue 1, jan.1991
 http://www.naturalnews.com/033498_SerratioPeptidase_inflammation.html